The ability to administer biologically effective drugs that are poorly soluble in biocompatible solvents to mammals has been a major hurdle in the realm of pharmaceutical and medicinal chemistry. In particular, difficulties arise when an active drug is either insoluble in water or unstable in other biocompatible solvents. Solubility problems are common and often cause delays in drug development. Several technologies have been developed to facilitate the delivery of poorly soluble and insoluble compounds. Examples of technologies specifically designed to solve solubility problems include complexing agents, nanoparticles, microemulsions, solubility enhancing formulations, prodrugs and water soluble prodrugs, and novel polymer systems.
One way to improve the solubility of medicinal agents is to chemically modify them or conjugate them to another molecule to alter the solubility profile in a particular solvent. Conjugates of active drugs, often referred to as prodrugs, include a chemical derivative of a biologically-active parent compound. Prodrugs may be biologically inert or maintain activity that is substantially less than the parent or active compound. The parent compound is released from the prodrug in vivo by a variety of mechanisms, including, for example, hydrolysis or enzymatic cleavage. The rate of release is influenced by several factors, including the type of chemical bond joining the active parent drug to the conjugate moiety.
Potent drugs that are poorly soluble in water include camptothecin and its analogs, taxanes (e.g., paclitaxel, docetaxel), candesartan, amphotericin B, azathioprine, cyclosporine, entacapone, danazol, eletriptan, and bosentan, to name a few. There continues to be a need for new methods, which are both safe and effective, of solubilizing and delivering poorly soluble active drug molecules.